Our goal in this proposal is to produce an FDA-approved image-guidance platform for use with MRI or ultrasound to be used sequentially from baseline imaging through prostate biopsy for diagnosis and treatment (brachytherapy) of prostate cancer. Today, the most common diagnostic method for prostate cancer, transrectal ultrasound (TRUS)-guided biopsy, misses cancer a significant percentage of the time. We, therefore, propose to develop an MR/US imaging platform that uses robotic assistance for precise needle placement in two interventions: transperineal biopsy-guided using either a combination of MR or TRUS and MR-guided brachytherapy with an aim to better identify, target, and treat cancer with fewer side effects. Our approach has the capabilities for dynamic, precise, and quantitative evaluation of biopsy needle or needle and source (seed) position and target dosimetry during the course of a brachytherapy procedure. We believe these capabilities can improve overall biopsy yield and/or quality of therapy (improved dosage, reduced morbidity and toxicity). In our process, cancer treatment will benefit from biopsy-confirmed tumor locations that allow for dose escalation and modification of a treatment plan based upon histological mapping of cancer locations. First and second generation devices with software programs have already been developed. In the next cycle, we will develop MR/US registration algorithms and MR/US tissue classification to extend our approaches beyond MR to the more ubiquitous modality of US. We will re-design and validate a remotely actuated master-slave robotic with haptic feedback for needle placement during biopsy and brachytherapy. A physician will fully control the "slave" robot in the bore of the MRI scanner by operating a "master" robotic interface next to the bore for more precise needle placement in biopsies and brachytherapy compared to TRUS- or MR-guided manual approaches. A master/slave robotic device, based upon our first cycle work, will be at the Brigham and Women's Hospital's new image guided therapy suite, the AMIGO, that contains a 3T wide bore magnet. 3T MRI techniques have become a mainstay of all MR imaging protocols at the Brigham, and in the first cycle we have established a 3T template-based transperineal biopsy program. In addition to our supportive preliminary data, we are well prepared to move forward because we have assembled a team with the expertise needed to successfully complete all phases of the research. Our longer term goal, which extends beyond this proposal, is to establish a platform for precise needle placement into image-defined lesions to allow for image-guided molecular diagnostics. By this we mean, ultimately any imaging study, traditional or molecular (e.g PET with C- 11 tracers), can be registered with the techniques we propose here and sampled using our robotic approach. In pursuit of this we would collaborate with the Pathology Core at the Dana Farber-Harvard Cancer Center (NCI center) to begin investigating the phenotypic (imaging) correlates with prostate pathological genomics. PUBLIC HEALTH RELEVANCE: Prostate care for prostate cancer, the most common cancer in men, is lacking given that TRUS, the most common diagnostic method for prostate cancer, misses cancer a significant percentage of the time. This R01 fills in a wide gap in public health by creating an image-guided system capable of focal image-defined targeted biopsy sampling and radiation therapy that will move to FDA device application and approval during this grant cycle. Such a system provides more targeted sampling for better understanding of prostate cancer and targeting and planning of therapy including radiation dosing during brachytherapy and, further, in the new cycle, TRUS can be optimized with MR parameters that are achievable at 3 Tesla that can provide information about focal cancers, and how to best treat them with minimal side-effects.